Soligenix announced long-term follow-up data from its recent positive Phase 2 clinical trial, in which SGX942 (dusquetide) demonstrated a significant reduction in the median duration of severe oral mucositis in patients with head and neck cancer (HNC), have been published in the peer-reviewed journal Biotechnology Reports. These 12-month data further support the safety and tolerability of SGX942, with the 1.5 mg/kg treatment group demonstrating accelerated tumor resolution and a decreased mortality rate relative to the placebo group.
As a first-in-class innate defense regulator (IDR), dusquetide modulates the innate immune system, enhancing its tissue-healing and anti-infective mechanisms and decreasing the often deleterious inflammatory responses. The pathogenesis of oral mucositis involves the dysregulation of the innate immune system. In a randomized, double-blind, placebo-controlled Phase 2 clinical trial in 111 patients, SGX942 (1.5 mg/kg dusquetide) successfully reduced the median duration of severe oral mucositis when compared to placebo by 50% in all patients, and by 67% in patients receiving the most aggressive chemoradiation therapy (CRT) for treatment of their HNC. In addition to the oral mucositis findings, decreases in the bacterial infection rate were observed with SGX942 treatment, along with an increased incidence of "complete response" of tumor at the one month follow-up visit and a reduction in opioid pain medication use.
Long-term follow-up data indicate that the tumor resolution was enduring and, moreover, that the mortality rate in the SGX942 1.5 mg/kg treatment group was lower (p=0.08) than the placebo group over the 12 months following completion of CRT. These data further support the safety and tolerability of SGX942 in this patient population. Potential ancillary benefits of utilizing SGX942 for the treatment of oral mucositis include the reduction of infection, the accelerated tumor resolution and the decreased mortality rate.
Soligenix recently announced that it has received US Food and Drug Administration (FDA) clearance to advance the pivotal Phase 3 clinical trial and released the protocol study design for SGX942, following the completion of the Phase 2 follow-up visits late last year. The Phase 3 study utilizes the patient population at highest risk of severe oral mucositis as identified in the Phase 2 study. While the drug effect was 67% in the Phase 2 study, a much more conservative estimate was utilized in planning the Phase 3 study, yielding a study size of approximately 190 subjects. SGX942 will be administered in conjunction with the CRT, as a treatment for oral mucositis.
"The long-term follow-up data further support the safety and tolerability of SGX942, consistent with the results from the previous Phase 1 study," Richard Straube, MD, Senior Vice President and Chief Medical Officer of Soligenix said. "The Phase 2 study also enabled a highly powered and efficient Phase 3 study to be designed, which will use duration of severe oral mucositis as the primary endpoint, while continuing to assess incidence of infection, tumor resolution status and survival as important safety endpoints. We look forward to starting the pivotal Phase 3 study this year."
The Phase 2 oral mucositis clinical study was partially funded with a grant from the National Institute of Dental and Craniofacial Research Small Business Innovation Research grant #1R43 DE024032-01.
Dusquetide (the active ingredient in SGX942) is an IDR, a new class of short, synthetic peptides. It has a novel mechanism of action whereby it modulates the body's reaction to both injury and infection towards an anti-inflammatory and an anti-infective response. IDRs have no direct antibiotic activity but, by modulating the host's innate immune system responses, increase survival after infections caused by a broad range of bacterial Gram-negative and Gram-positive pathogens. It also accelerates resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- and/or radiation therapy. Preclinical efficacy and safety has been demonstrated in numerous animal disease models including mucositis, colitis, melioidosis, macrophage activation syndrome (MAS) and other bacterial infections.
SGX942 has demonstrated safety in a Phase 1 clinical study in 84 healthy human volunteers. Recently, SGX942 had positive results in an exploratory Phase 2 clinical study in 111 patients with oral mucositis due to CRT for HNC. Consistent with preclinical findings, SGX942 at a dose of 1.5 mg/kg demonstrated positive improvements in decreasing the duration of severe oral mucositis by 50% overall compared to the placebo group, from 18 days to 9 days (p=0.099). In patients at the highest risk of developing severe oral mucositis, the reduction in the duration of severe oral mucositis was even more significant at 67% when treated with SGX942 1.5 mg/kg, from 30 days to 10 days (p=0.04). The p-values met the prospectively defined statistical threshold of p<0.1 in the study protocol. Additional observations included an improved tumor response to CRT at the one month follow-up visit, as well as decreases in mortality and infection rate.
Long-term (12 month) follow-up data further indicated the safety and tolerability of SGX942 treatment, with a sustained trend towards reduced mortality and increased tumor resolution in the 1.5 mg/kg SGX942 treatment group compared to the placebo group. Opioid pain medication use was also seen to decrease over the course of CRT in the 1.5 mg/kg SGX942 treatment group at the point of highest oral mucositis risk, while it increased in the placebo group.
The Phase 2 oral mucositis clinical study was partially funded with a grant from the National Institute of Dental and Craniofacial Research Small Business Innovation Research grant #1R43 DE024032-01.
Drug products containing dusquetide have also received Fast Track Designations from the FDA for the treatment of oral mucositis as a result of radiation and/or chemotherapy treatment in HNC patients, and as an adjunctive therapy with other antibacterial drugs, for the treatment of melioidosis. Orphan Drug Designations for use of dusquetide in the treatment of MAS as well as for the treatment of acute radiation syndrome have also been granted. In addition, dusquetide has been granted Promising Innovative Medicine designation in the United Kingdom by the Medicines and Healthcare Products Regulatory Agency for the treatment of severe oral mucositis in HNC patients receiving CRT.